title: The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease.
abstract: OBJECTIVE
  To determine whether aspirin and antioxidant therapy, combined or alone, are more effective than placebo in reducing the development of cardiovascular events in patients with diabetes mellitus and asymptomatic peripheral arterial disease.
  
  
  METHODS
  Multicentre, randomised, double blind, 2x2 factorial, placebo controlled trial.
  
  
  METHODS
  16 hospital centres in Scotland, supported by 188 primary care groups.
  
  
  METHODS
  1276 adults aged 40 or more with type 1 or type 2 diabetes and an ankle brachial pressure index of 0.99 or less but no symptomatic cardiovascular disease.
  
  
  METHODS
  Daily, 100 mg aspirin tablet plus antioxidant capsule (n=320), aspirin tablet plus placebo capsule (n=318), placebo tablet plus antioxidant capsule (n=320), or placebo tablet plus placebo capsule (n=318).
  
  
  METHODS
  Two hierarchical composite primary end points of death from coronary heart disease or stroke, non-fatal myocardial infarction or stroke, or amputation above the ankle for critical limb ischaemia; and death from coronary heart disease or stroke.
  
  
  RESULTS
  No evidence was found of any interaction between aspirin and antioxidant. Overall, 116 of 638 primary events occurred in the aspirin groups compared with 117 of 638 in the no aspirin groups (18.2% v 18.3%): hazard ratio 0.98 (95% confidence interval 0.76 to 1.26). Forty three deaths from coronary heart disease or stroke occurred in the aspirin groups compared with 35 in the no aspirin groups (6.7% v 5.5%): 1.23 (0.79 to 1.93). Among the antioxidant groups 117 of 640 (18.3%) primary events occurred compared with 116 of 636 (18.2%) in the no antioxidant groups (1.03, 0.79 to 1.33). Forty two (6.6%) deaths from coronary heart disease or stroke occurred in the antioxidant groups compared with 36 (5.7%) in the no antioxidant groups (1.21, 0.78 to 1.89).
  
  
  CONCLUSIONS
  This trial does not provide evidence to support the use of aspirin or antioxidants in primary prevention of cardiovascular events and mortality in the population with diabetes studied.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN53295293.
authors.affiliation: Institute of Cardiovascular Research, University of Dundee, Ninewells Hospital, Dundee DD1 9SY. J.J.F.Belch@dundee.ac.uk
authors.forename: Jill
authors.initials: J
authors.lastname: Belch
authors.forename: Angus
authors.initials: A
authors.lastname: MacCuish
authors.forename: Iain
authors.initials: I
authors.lastname: Campbell
authors.forename: Stuart
authors.initials: S
authors.lastname: Cobbe
authors.forename: Roy
authors.initials: R
authors.lastname: Taylor
authors.forename: Robin
authors.initials: R
authors.lastname: Prescott
authors.forename: Robert
authors.initials: R
authors.lastname: Lee
authors.forename: Jean
authors.initials: J
authors.lastname: Bancroft
authors.forename: Shirley
authors.initials: S
authors.lastname: MacEwan
authors.forename: James
authors.initials: J
authors.lastname: Shepherd
authors.forename: Peter
authors.initials: P
authors.lastname: Macfarlane
authors.forename: Andrew
authors.initials: A
authors.lastname: Morris
authors.forename: Roland
authors.initials: R
authors.lastname: Jung
authors.forename: Christopher
authors.initials: C
authors.lastname: Kelly
authors.forename: Alan
authors.initials: A
authors.lastname: Connacher
authors.forename: Norman
authors.initials: N
authors.lastname: Peden
authors.forename: Andrew
authors.initials: A
authors.lastname: Jamieson
authors.forename: David
authors.initials: D
authors.lastname: Matthews
authors.forename: Graeme
authors.initials: G
authors.lastname: Leese
authors.forename: John
authors.initials: J
authors.lastname: McKnight
authors.forename: Iain
authors.initials: I
authors.lastname: O'Brien
authors.forename: Colin
authors.initials: C
authors.lastname: Semple
authors.forename: John
authors.initials: J
authors.lastname: Petrie
authors.forename: Derek
authors.initials: D
authors.lastname: Gordon
authors.forename: Stuart
authors.initials: S
authors.lastname: Pringle
authors.forename: Ron
authors.initials: R
authors.lastname: MacWalter
mesh_terms: D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control*; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000517:prevention & control*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D010975:Platelet Aggregation Inhibitors; D001241:Aspirin